Device and method for monitoring body fluid and electrolyte disorders

ABSTRACT

A device and a method for measuring body fluid-related metrics using spectrophotometry to facilitate therapeutic interventions aimed at restoring body fluid balance. The specific body fluid-related metrics include the absolute volume fraction of water in the extravascular and intravascular tissue compartments, as well as the shifts of water between these two compartments. The absolute volume fraction of water is determined using algorithms where received radiation measured at two or more wavelengths are combined to form either a single ratio, a sum of ratios or ratio of ratios of the form log[R(λ 1 )/R(λ 2 )] in which the received radiation in the numerator depends primarily on the absorbance of water and the received radiation in the denominator depends primarily on the absorbance of water and the sum of the absorbances of non-heme proteins, lipids and water in tissue. The difference between the fraction of water in the intravascular fluid volume (“IFV”) and extravascular fluid volume (“EFV”) compartments are also determined using a differential method that takes advantage of the observation that pulsations caused by expansion of blood vessels in the skin as the heart beats produce changes in the received radiation at a particular wavelength that are proportional to the difference between the effective absorption of light in the blood and the surrounding tissue. This difference, integrated over time, provides a measure of the quantity of the fluid that shifts into and out of the capillaries. A mechanism for mechanically inducing a pulse is built into the device to improve the reliability of measurements of IFV−EFV under weak-pulse conditions.

BACKGROUND OF THE INVENTION

The maintenance of body fluid balance is of foremost concern in the careand treatment of critically ill patients, yet physicians have access tofew diagnostic tools to assist them in this vital task. Patients withcongestive heart failure, for example, frequently suffer from chronicsystemic edema, which must be controlled within tight limits to ensureadequate tissue perfusion and prevent dangerous electrolytedisturbances. Dehydration of infants and children suffering fromdiarrhea can be life-threatening if not recognized and treated promptly.

The most common method for judging the severity of edema or dehydrationis based on the interpretation of subjective clinical signs (e.g.,swelling of limbs, dry mucous membranes), with additional informationprovided by measurements of the frequency of urination, heart rate,serum urea nitrogen SUN/creatinine ratios, and blood electrolyte levels.None of these variables alone, however, is a direct and quantitativemeasure of water retention or loss.

The indicator-dilution technique, which provides the most accuratedirect measure of water in body tissues, is the present de factostandard for assessment of body fluid distribution. It is, however, aninvasive technique that requires blood sampling. Additionally, a numberof patents have disclosed designs of electrical impedance monitors formeasurement of total body water. The electrical-impedance technique isbased on measuring changes in the high-frequency (typically 10 KHz-1MHz) electrical impedance of a portion of the body. Mixed results havebeen obtained with the electrical-impedance technique in clinicalstudies of body fluid disturbances as reported by various investigators.The rather poor accuracy of the technique seen in many studies point tounresolved deficiencies of these designs when applied in a clinicalsetting.

Therefore, there exists a need for methods and devices for monitoringtotal body water fractions which do not suffer from problems due totheir being invasive, subjective and inaccurate.

SUMMARY OF THE INVENTION

Embodiments of the present invention provide devices and methods thatmeasure body fluid-related metrics using spectrophotometry to facilitatetherapeutic interventions aimed at restoring body fluid balance. Thespecific body fluid-related metrics include the absolute volume fractionof water in the extravascular and intravascular tissue compartments, aswell as the shifts of water between these two compartments. The absolutevolume fraction of water is determined using algorithms where receivedradiation measured at two or more wavelengths are combined to formeither a single ratio, a sum of ratios or ratio of ratios of the formlog[R(λ₁)/R(λ₂)] in which the received radiation in the numeratordepends primarily on the absorbance of water and the received radiationin the denominator depends primarily on the absorbance of water and thesum of the absorbances of non-heme proteins and lipids in tissue.

The difference between the fraction of water in the intravascular fluidvolume (“IFV”) and extravascular fluid volume (“EFV”) compartments arealso determined using a differential method that takes advantage of theobservation that pulsations caused by expansion of blood vessels in theskin, as the heart beats, produce changes in the received radiation at aparticular wavelength that are proportional to the difference betweenthe effective absorption of light in the blood and the surroundingtissue. This difference, integrated over time, provides a measure of thequantity of the fluid that shifts into and out of the capillaries. Amechanism for mechanically inducing a pulse is built into the device toimprove the reliability of measurements of IFV−EFV under weak-pulseconditions.

For a fuller understanding of the nature and advantages of theembodiments of the present invention, reference should be made to thefollowing detailed description taken in conjunction with theaccompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph showing tissue water fraction measured on the ear of apig during an experiment using reflectance measurements at twowavelengths.

FIG. 2 is a graph showing an example regression for prediction of waterfrom reflectances measured at three wavelengths.

FIG. 3 is a graph showing an example regression of a two-wavelengthalgorithm for determination of the difference between the intravascularand extravascular water fraction from pulsatile reflectances measuredtwo wavelengths.

FIG. 4 is a diagram of an intermittent-mode version of a fluid monitor.

FIG. 5 is a diagram of a continuous-mode version of a fluid monitor.

FIG. 6 is a block diagram of a handheld apparatus for noninvasivemeasurement and display of tissue water.

DESCRIPTION OF THE SPECIFIC EMBODIMENTS

Embodiments of the present invention overcome the problems ofinvasiveness, subjectivity, and inaccuracy from which previous methodsfor body fluid assessment have suffered. The method of diffusereflectance near-infrared (“NIR”) spectroscopy is employed to measurethe absolute fraction of water in skin. An increase or decrease in thefree (non protein-bound) water content of the skin produces uniquealterations of its NIR reflectance spectrum in three primary bands ofwavelengths-(1100-1350 nm, 1500-1800 nm, and 2000-2300 nm) in whichnone-heme proteins (primarily collagen and elastin), lipids, and waterabsorb. According to the results of numerical simulations andexperimental studies carried out by the inventor, the tissue waterfraction f_(w), defined spectroscopically as the ratio of the absorbanceof water and the sum of the absorbances of none-heme proteins, lipids,and water in the tissue, can be measured accurately in the presence ofnonspecific scattering variation, temperature, and other interferingvariables.

In embodiments of this invention, the apparatus and its associatedmeasurement algorithm are designed according to the followingguidelines:

-   -   1. To avoid the shunting of light through the superficial layers        of the epidermis, the light source and detector in optical        reflectance probe have low numerical apertures, typically less        than 0.3.    -   2. The spacing between the source and detector in the probe is        in the range of 1-5 mm to confine the light primarily to the        dermis.    -   3. The reflectances are measured at wavelengths greater than        1150 nm to reduce the influence of hemoglobin absorption.    -   4. To ensure that the expression that relates the measured        reflectances and f_(w) yields estimates of water fraction that        are insensitive to scattering variations, the lengths of the        optical paths through the dermis at the wavelengths at which the        reflectances are measured are matched as closely as possible.        This matching is achieved by judicious selection of wavelength        sets that have similar water absorption characteristics. Such        wavelength sets may be selected from any one of the three        primary wavelength bands (1100-1350 nm, 1500-1800 nm, and        2000-2300 nm) discussed above. Wavelength pairs or sets are        chosen from within one of these three primary bands, and not        from across the bands. More particularly the wavelength pair of        1180 and 1300 nm are one such wavelength set where the lengths        of the optical paths through the dermis at these wavelengths are        matched as closely as possible.    -   5. To ensure that the expression that relates the measured        reflectances and f_(w) yields estimates of water fraction that        are insensitive to temperature variations, the wavelengths at        which the reflectances are measured are chosen to be either        close to temperature isosbestic wavelengths in the water        absorption spectrum or the reflectances are combined in a way        that cancels the temperature dependencies of the individual        reflectances. Typically, absorption peaks of various biological        tissue components may shift with variations in temperature.        Here, wavelengths are selected at points in the absorption        spectrum where no significant temperature shift occurs.        Alternately, by knowing the value of this temperature shift,        wavelength sets may be chosen such that any temperature shift is        mathematically canceled out when optical measurements are        combined to compute the value of a tissue water metric. Such        wavelength sets may be selected from any one of the three        primary wavelength bands (1100-1350 nm, 1500-1800 nm, and        2000-2300 nm) discussed above. Wavelength pairs or sets are        chosen from within one of these three primary bands, and not        from across the bands. More particularly the wavelength pair of        1180 and 1300 nm are one such pair of temperature isosbestic        wavelengths in the water absorption spectrum.    -   6. The reflectances measured at two or more wavelengths are        combined to form either a single ratio, a sum of ratios or ratio        of ratios of the form log[R(λ₁)/R(λ₂)] in which the reflectance        in the numerator depends primarily on the absorbance of water        and the reflectance in the denominator is nearly independent of        the fraction of solids (lipids and proteins) in the tissue.

Thus, in one embodiment of the present invention the water fraction,f_(w) is estimated according to the following equation, based on themeasurement of reflectances, R(λ) at two wavelengths and the empiricallychosen calibration constants c₀ and c₁:f _(w) =c ₁ log[R(λ₁)/R(λ₂)]+c ₀   (1)

Numerical simulations and in vitro experiments indicate that f_(w) canbe estimated with an accuracy of approximately ±2% over a range of watercontents between 50 and 80% using Equation (1), with reflectances R(λ)measured at two wavelengths and the calibration constants c₀ and c₁chosen empirically. Examples of suitable wavelength pairs are λ₁=1300nm, λ₂=1168 nm, and λ₁=1230 nm, λ₂=1168 nm.

The ability to measure changes in the water content in the ear of a pigusing two-wavelength NIR reflectometry was demonstrated experimentallyin a study in which a massive hemorrhage was induced in a pig and thelost blood was replaced with lactated Ringer's solution over a period ofseveral hours. Ringer's solution is a well-known solution of salts inboiled and purified water. FIG. 1 shows the water fraction in the skinof the ear of a pig, measured using Equation (1) with λ₁=1300 nm andλ₂=1168 nm. Referring to FIG. 1, it should be noted that experimentalobservations of concern to this embodiment commence when the lactatedRinger's solution was infused 120 minutes after the start of theexperiment. It should also be noted that the drift in the water fractionfrom approximately 77.5% to 75% before the infusion is not related tothis infusion experiment, but is related to the base-line hemorrhageportion of the experiment. The results show that the method of thepresent embodiment correctly reflects the effect of the infusion byshowing an increase in tissue water fraction from approximately 75% to79% while the infusion is continuing. These data suggest that thedisclosed embodiment has a clear value as a monitor of rehydrationtherapy in a critical care setting.

In another embodiment of the present invention the water fraction, f_(w)is estimated according to Equation (2) below, based on the measurementof reflectances, R(λ) at three wavelengths and the empirically chosencalibration constants c₀, c₁ and c₂:f _(w) =c ₂ log[R(λ₁)/R(λ₂)]+c ₁ log[R(λ₂)/R(λ₃)]+c ₀   (2)

Better absolute accuracy can be attained using Equation (2) whichincorporates reflectance measurements at an additional wavelength. Theresults of in vitro experiments on excised skin indicate that thewavelength triple (λ₁=1190 nm, λ₂=1170 nm, λ₃=1274 nm) yields accurateestimates of skin water content based on Equation (2).

In yet another embodiment of the present invention the water fraction,f_(w) is estimated according to Equation (3) below, based on themeasurement of reflectances, R(λ) at three wavelengths and theempirically chosen calibration constants c₀ and c₁: $\begin{matrix}{f_{w} = {{c_{1}\frac{\log\left\lbrack {{R\left( \lambda_{1} \right)}/{R\left( \lambda_{2} \right)}} \right\rbrack}{\log\left\lbrack {{R\left( \lambda_{3} \right)}/{R\left( \lambda_{2} \right)}} \right\rbrack}} + c_{0}}} & (3)\end{matrix}$

Better absolute accuracy can be attained using Equations (3), as isattained using Equations (2), which also incorporates reflectancemeasurements at an additional wavelength. Numerical simulations as shownin FIG. 2 indicate that an accuracy better than ±0.5% can be achievedusing Equation (3), with reflectances measured at three closely spacedwavelengths: λ₁=1710 nm, λ₂=1730 nm, and λ₃=1740 nm.

Individuals skilled in the art of near-infrared spectroscopy wouldrecognize that, provided that the aforementioned guidelines arefollowed, additional terms can be added to Equations (1)-(3) toincorporate reflectance measurements made at more than three wavelengthsand thus improve accuracy further.

An additional embodiment of the disclosed invention provides the abilityto quantify shifts of fluid into and out of the bloodstream through anovel application of pulse spectrophotometry. This additional embodimenttakes advantage of the observation that pulsations caused by expansionof blood vessels in the skin as the heart beats produce changes in thereflectance at a particular wavelength that are proportional to thedifference between the effective absorption of light in the blood andthe surrounding interstitial tissues. Numerical simulation indicatethat, if wavelengths are chosen at which water absorption issufficiently strong, the difference between the fractions of water inthe blood, f_(w) ^(blood) and surrounding tissue, f_(w) ^(tissue) isproportional to the ratio of the dc-normalized reflectance changes(ΔR/R) measured at two wavelengths, according to Equation (4) below:$\begin{matrix}{{{f_{w}^{blood} - f_{w}^{tissue}} = {{{c_{1}\left( \frac{\Delta\quad R}{R} \right)}_{\lambda_{1}}/\left( \frac{\Delta\quad R}{R} \right)_{\lambda_{2}}} + c_{0}}},} & (4)\end{matrix}$

where c₀ and c₁ are empirically determined calibration constants. Thisdifference, integrated over time, provides a measure of the quantity offluid that shifts into and out of the capillaries. FIG. 3 shows theprediction accuracy expected for the wavelength pair λ₁=1320 nm andλ₂=1160 nm.

FIGS. 4 and 5 show diagrams of two different versions of an instrumentfor measuring the amount of water in body tissues. The simplest versionof the instrument 400 shown in FIG. 4 is designed for handheld operationand functions as a spot checker. Pressing the spring-loaded probe head410 against the skin 412 automatically activates the display of percenttissue water 414. The use of the spring-loaded probe head provides theadvantages of automatically activating the display device when neededand turning the device off when not in use, thereby extending device andbattery life. Moreover, this unique use of a spring-loaded probe alsoprovides the force needed to improve the reliability of measurements.Percent tissue water represents the absolute percentage of water in theskin beneath the probe (typically in the range 0.6-0.9). The forceexerted by a spring or hydraulic mechanism (not shown) inside the probehead 410 pushes out most of the blood in the skin below the probe toreduce the error caused by averaging the intravascular and extravascularfluid fractions. A pressure transducer (not shown) within the probe head410 measures the compressibility of the skin for deriving an index ofthe fraction of free (mobile) water.

The more advanced version of the fluid monitor 500 shown in FIG. 5 isdesigned for use as a critical-care monitor. In addition to providing acontinuous display of the absolute volume fraction of water 510 at thesite of measurement 512, it also provides a trend display of thetime-averaged difference between the intravascular fluid volume (“IFV”)and extravascular fluid volume (“EFV”) fractions 514, updated every fewseconds. This latter feature would give the physician immediate feedbackon the net movement of water into or out of the blood and permit rapidevaluation of the effectiveness of diuretic or rehydration therapy. Tomeasure the IFV−EFV difference, the monitor records blood pulses in amanner similar to a pulse oximeter. Therefore, placement of the probe onthe finger or other well-perfused area of the body would be required. Incases in which perfusion is too poor to obtain reliable pulse signals,the IFV−EFV display would be blanked, but the extravascular waterfraction would continue to be displayed. A mechanism for mechanicallyinducing the pulse is built into the probe to improve the reliability ofthe measurement of IFV−EFV under weak-pulse conditions.

FIG. 6. is a block diagram of a handheld device 600 for measuring tissuewater fraction within the IFV and the EFV, as well as shifts in waterbetween these two compartments with a pulse inducing mechanism. Usingthis device 600, patient places his/her finger 610 in the probe housing.Rotary solenoid 612 acting through linkage 614 and collar 616 induces amechanical pulse to improve the reliability of the measurement ofIFV−EFV. LEDs 618 emit light at selected wavelengths and photodiode 620measure the transmitted light. Alternately, the photodiode 620 can beplaced adjacent to the LEDs to allow for the measurement of thereflectance of the emitted light. Preamplifier 622 magnifies thedetected signal for processing by the microprocessor 624. Microprocessor624, using algorithms described above, determines the tissue waterfraction within the IFV and the EFV, as well as shifts in water betweenthese two compartments, and prepares this information for display ondisplay device 626. Microprocessor 624 is also programmed to handle theappropriate timing between the rotary solenoid's operation and thesignal acquisition and processing. The design of the device and themicroprocessor integrates the method and apparatus for reducing theeffect of noise on measuring physiological parameters as described inU.S. Pat. No.5,853,364, assigned to Nellcor Puritan Bennett, Inc., now adivision of the assignee of the present invention, the entire disclosureof which is hereby incorporated herein by reference. Additionally, thedesign of the device and the microprocessor also integrates theelectronic processor as described in U.S. Pat. No. 5,348,004, assignedto Nellcor Incorporated, now a division of the assignee of the presentinvention, the entire disclosure of which is hereby incorporated hereinby reference.

As will be understood by those skilled in the art, other equivalent oralternative methods for the measurement of tissue water fraction withinthe IFV and the EFV, as well as shifts in water between these twocompartments according to the embodiments of the present invention canbe envisioned without departing from the essential characteristicsthereof. For example, the device can be operated in either a handheld ora tabletop mode, and it can be operated intermittently or continuously.Moreover, individuals skilled in the art of near-infrared spectroscopywould recognize that additional terms can be added to the algorithmsused herein to incorporate reflectance measurements made at more thanthree wavelengths and thus improve accuracy further. Also, light sourcesor light emission optics other then LED's including and not limited toincandescent light and narrowband light sources appropriately tuned tothe desired wavelengths and associated light detection optics may beplaced within the probe housing which is placed near the tissue locationor may be positioned within a remote unit; and which deliver light toand receive light from the probe location via optical fibers.Additionally, although the specification describes embodimentsfunctioning in a back-scattering or a reflection mode to make opticalmeasurements of reflectances, other embodiments can be working in aforward-scattering or a transmission mode to make these measurements.These equivalents and alternatives along with obvious changes andmodifications are intended to be included within the scope of thepresent invention. Accordingly, the foregoing disclosure is intended tobe illustrative, but not limiting, of the scope of the invention whichis set forth in the following claims.

1. A sensor comprising: a probe housing configured to be placedproximate to a tissue location to be monitored; light emission opticsoperatively coupled to the housing and configured to direct radiation atthe tissue location; light detection optics operatively coupled to thehousing and configured to receive radiation from the tissue location;and a mechanism connected to the housing and configured to induce apulse mechanically.
 2. The device of claim 1, wherein the mechanismcomprises: a collar configured to encircle the tissue location; and alinkage configured to decrease and increase the circumference of thecollar.
 3. The device of claim 2, comprising a rotary solenoidoperatively coupled to the linkage to cause the linkage to decrease andincrease the circumference of the collar.
 4. The device of claim 1,wherein the light emission optics and the light detection optics arearranged to confine the light primarily to a dermis portion of thetissue location.
 5. The device of claim 1, wherein the light emissionoptics and the light detection optics are separated within the range of1 to 5 mm.
 6. A sensor comprising: a probe housing configured to beplaced proximate to a tissue location to be monitored; light emissionoptics operatively coupled to the housing and configured to directradiation at the tissue location; light detection optics operativelycoupled to the housing and configured to receive radiation from thetissue location; and a mechanism coupled to the housing and configuredto apply a force proximate to the tissue location, wherein the mechanismis configured to automatically activate the light emission optics whenthe force is applied.
 7. The device of claim 6, wherein the mechanismcomprises a spring-loaded probe head.
 8. The device of claim 6, whereinthe force is such that a fluid content of the tissue location is notaffected to a measurable degree.
 9. The device of claim 6, wherein theforce exerted by the mechanism is sufficient to push blood out of thetissue location such that the tissue location is substantiallyextravascular.
 10. A sensor comprising: a housing configured to beplaced proximal to a tissue location to be monitored; an occlusiondevice coupled to the housing and configured to magnify a fractionalchange in vascular blood volume to a value greater than a fractionalchange produced by normal arterial pulsations; light emission opticsoperatively coupled to the housing and configured to direct radiation atthe tissue location; and light detection optics operatively coupled tothe housing and configured to receive radiation from the tissuelocation.
 11. A device for determining body fluid-related metrics, thedevice comprising: a processing device configured to process a signalindicative of radiation received from a tissue location to compute thebody fluid-related metrics, wherein the body fluid-related metricscomprise absolute volume fractions of water in extravascular andintravascular bodily tissue compartments and differences betweenintravascular fluid volume and extravascular fluid volume fractions. 12.The device of claim 11, comprising a display device coupled to theprocessing device and configured to display the body fluid-relatedmetrics.
 13. The device of claim 11, wherein the processing devicereceives and compares at least two sets of optical measurements, wherethe at least first set of optical measurements corresponds to thedetection of the radiation whose absorption is primarily due to water,lipids and non-heme proteins, and where the at least second set ofoptical measurements corresponds to the detection of the radiation whoseabsorption is primarily due to water, and where a comparison of the atleast two optical measurements provides a measure of the absolute waterfraction within the tissue location.
 14. The device of claim 11, whereinthe processing device receives and compares at least two sets of opticalmeasurements, where the at least two sets of optical measurements arebased on the received radiation from at least two wavelengths and whichare combined to form either a single ratio of the received radiation, asum of ratios of the received radiation, or ratios of ratios of thereceived radiation.
 15. The device of claim 11, wherein the processingdevice receives and compares at least two sets of optical measurementsfrom at least two different wavelengths, where absorption of light atthe at least two different wavelengths is primarily due to water whichis in vascular blood and in extravascular tissue, and where a ratio ofthe at least two measurements provides a measure of a difference betweenfractions of water in the blood and the tissue location.
 16. A devicefor determining body fluid-related metrics, the device comprising: aprocessing device configured to process a signal indicative of radiationreceived from a tissue location to compute the body fluid-relatedmetrics; a display device coupled to the processing device andconfigured to automatically display the body fluid-related metrics inresponse to receiving a signal from a probe, the signal from the probebeing indicative of the probe being pressed against the tissue location.17. A sensor comprising: a housing configured to be placed proximal to atissue location to be monitored; light emission optics operativelycoupled to the housing and configured to direct radiation at the tissuelocation; light detection optics operatively coupled to the housing andconfigured to receive radiation from the tissue location; and amechanism coupled to the housing and configured to mechanically inducinga pulse within the tissue location to facilitate measurements ofdifferences between an intravascular fluid volume and an extravascularfluid volume fractions under weak-pulse conditions.
 18. A device fordetermining body fluid-related metrics, the device comprising: aprocessing device configured to process a signal indicative of radiationreceived from a tissue location to compute the body fluid-relatedmetrics, the body fluid-related metrics comprising percent body waterand a water balance, where the water balance is an integrated differencebetween a water fraction in blood and a water fraction in extravasculartissue.
 19. A device for determining an absolute volume fraction ofwater within human tissue, the device comprising: a processing deviceconfigured to process a signal indicative of radiation received from atissue location to compute the absolute volume fraction of water,wherein the processing device receives and compares at least two sets ofoptical measurements, where the at least first set of opticalmeasurements corresponds to the detection of the radiation whoseabsorption is primarily due to water, lipids and non-heme proteins, andwhere the at least second set of optical measurements corresponds to thedetection of the radiation whose absorption is primary due to water, andwhere a comparison of the at least two optical measurements provides ameasure of the absolute volume water fraction within the tissuelocation.
 20. A device for determining a difference between anintravascular fluid volume and an extravascular fluid volume, the devicecomprising: a processing device configured to process a signalindicative of radiation received from a tissue location to compute thedifference between an intravascular fluid volume and an extravascularfluid volume, wherein the processing device receives and compares atleast two sets of optical measurements from at least two differentwavelengths, where absorption of light at the at least two differentwavelengths is primarily due to water that is in vascular blood and inextravascular tissue, and where a comparison of the at least twomeasurements provides a measure of a difference between the fractions ofwater in the blood and the tissue location.
 21. A method for determiningbody fluid-related metrics in a human tissue location, the methodcomprising: processing a signal indicative of radiation received fromthe tissue location to compute the body fluid-related metrics, whereinthe body fluid-related metrics comprise absolute volume fractions ofwater in extravascular and intravascular bodily tissue compartments anddifferences between intravascular fluid volume and extravascular fluidvolume fraction.
 22. The method of claim 21, wherein the processingcomprises: measuring at least two sets of optical measurements based onreceived radiation of at least two wavelengths; combining the at leasttwo sets of optical measurements to form either a single ratio of thereceived radiation, a sum of ratios of the received radiation, or ratiosof ratios of the received radiation to form combinations of receivedradiation; and determining the metrics from the combinations.
 23. Adevice for determining body fluid-related metrics, the devicecomprising: a processing device configured to process a signalindicative of radiation received from a tissue location to compute thebody fluid-related metrics, wherein the radiation comprises a pluralityof spectral wavelengths chosen to be preferentially absorbed by tissuewater, non-heme proteins and lipids, where preferentially absorbedwavelengths are wavelengths whose absorption is substantiallyindependent of individual concentrations of non-heme proteins andlipids, and is substantially dependent on a sum of the individualconcentrations of non-heme proteins and lipids.
 24. The device of claim23, wherein the wavelengths are chosen to ensure that the receivedradiation is substantially insensitive to scattering variations and suchthat the optical path lengths through a dermis portion of the tissuelocation at the wavelengths are substantially equal.
 25. The device ofclaim 23, wherein the wavelengths are chosen to ensure that the receivedradiation from the tissue location is insensitive to temperaturevariations, where the wavelengths are temperature isosbestic in thewater absorption spectrum or individual wavelengths of the receivedradiation are combined in a way that substantially cancels temperaturedependencies of the individual wavelengths of the received radiationwhen computing tissue water fractions.
 26. The device of claim 23,wherein the wavelengths are chosen from one of three primary bands ofwavelengths of approximately 1100-1350 nm, approximately 1500-1800 nm,and approximately 2000-2300 nm.
 27. The device of claim 23, wherein theprocessing device receives and compares at least two sets of opticalmeasurements, where the at least first set of optical measurementscorresponds to the detection of the radiation whose absorption isprimarily due to water, lipids and non-heme proteins, and where the atleast second set of optical measurements corresponds to the detection ofthe radiation whose absorption is primarily due to water, and where acomparison of the at least two optical measurements provides a measureof the absolute water fraction within the tissue location.
 28. Thedevice of claim 23, wherein the processing device receives and comparesat least two sets of optical measurements, where the at least two setsof optical measurements are based on the received radiation from atleast two wavelengths and which are combined to form either a singleratio of the received radiation, a sum of ratios of the receivedradiation, or ratios of ratios of the received radiation.
 29. The deviceof claim 23, wherein the processing device receives and compares atleast two sets of optical measurements from at least two differentwavelengths, where absorption of light at the at least two differentwavelengths is primarily due to water which is in vascular blood and inextravascular tissue, and where a ratio of the at least two measurementsprovides a measure of a difference between fractions of water in theblood and the tissue location.
 30. The device of claim 23, wherein thebody fluid-related metrics comprise a tissue water fraction, where thetissue water fraction (f_(w)) is determined such thatf _(w) =c ₁ log[R(λ₁)/R(λ₂)]+c ₀, and where: calibration constants c₀and c₁ are chosen empirically; R(λ₁) is the received radiation at afirst wavelength; and R(λ₂) is the received radiation at a secondwavelength.
 31. The device of claim 30, wherein the first and secondwavelengths are approximately 1300 nm and approximately 1168 nm,respectively.
 32. The device of claim 30, wherein the first and secondwavelengths are approximately 1230 nm and approximately 1168 nm,respectively.
 33. The device of claim 23, wherein the body fluid-relatedmetrics comprise a tissue water fraction, and where the tissue waterfraction (f_(w)) is determined such thatf _(w) =c ₂ log[R(λ₁)/R(λ₂)]+c ₁ log[R(λ₂)/R(λ₃)]+c ₀, and where:calibration constants c₀, c₁ and c₂ are chosen empirically; R(λ₁) is thereceived radiation at a first wavelength; R(λ₂)is the received radiationat a second wavelength; and R(λ₃) is the received radiation at a thirdwavelength.
 34. The device of claim 33, wherein the first, second andthird wavelengths are approximately 1190 nm, approximately 1170 nm andapproximately 1274 nm, respectively.
 35. The device of claim 23, whereinthe body fluid-related metrics comprise a tissue water fraction, andwhere the tissue water fraction (f_(w)) is determined such that${f_{w} = {{c_{1}\frac{\log\left\lbrack {{R\left( \lambda_{1} \right)}/{R\left( \lambda_{2} \right)}} \right\rbrack}{\log\left\lbrack {{R\left( \lambda_{3} \right)}/{R\left( \lambda_{2} \right)}} \right\rbrack}} + c_{0}}},$and where: calibration constants c₀ and c₁ are chosen empirically; R(λ₁)is the received radiation at a first wavelength; R(λ₂) is the receivedradiation at a second wavelength; and R(λ₃) is the received radiation ata third wavelength.
 36. The device of claim 35, wherein the first,second and third wavelengths are approximately 1710 nm, approximately1730 nm and approximately 1740 nm, respectively.
 37. The device of claim23, wherein the body fluid-related metrics comprise a quantified measureof a difference between a water fraction in blood and a water fractionin extravascular tissue, where the difference is determined such that${{f_{w}^{blood} - f_{w}^{tissue}} = {{{c_{1}\left( \frac{\Delta\quad R}{R} \right)}_{\lambda_{1}}/\left( \frac{\Delta\quad R}{R} \right)_{\lambda_{2}}} + c_{0}}},$and where: f_(w) ^(blood) is the water fraction in the blood; f_(w)^(tissue) is the water fraction in the extravascular tissue; calibrationconstants c₀ and c₁ are chosen empirically; and$\left( \frac{\Delta\quad R}{R} \right)_{\lambda_{1}}/\left( \frac{\Delta\quad R}{R} \right)_{\lambda_{2}}$is a ratio of dc-normalized received radiation changes at a firstwavelength, λ₁ and a second wavelength, λ₂ respectively, where thereceived radiation changes are caused by a pulsation caused by expansionof blood vessels in tissue.
 38. The device of claim 37, wherein the bodyfluid-metrics comprise an integral of the difference between the waterfraction in the blood and the water fraction in the extravascular tissueto provide a measure of water that shifts into and out of capillaries inthe tissue location.
 39. The device of claim 37, wherein the first andsecond wavelengths are approximately 1320 nm and approximately 1160 nm,respectively.
 40. A device for determining body fluid-related metrics,the device comprising: a processing device configured to process asignal indicative of radiation received from a tissue location tocompute the body fluid-related metrics, wherein the body fluid-relatedmetrics comprises a tissue water fraction, and where the tissue waterfraction (f_(w)) is determined such that$f_{w} = {{c_{1}\frac{\log\left\lbrack {{R\left( \lambda_{1} \right)}/{R\left( \lambda_{2} \right)}} \right\rbrack}{\log\left\lbrack {{R\left( \lambda_{3} \right)}/{R\left( \lambda_{2} \right)}} \right\rbrack}} + c_{0}}$and where: calibration constants c₀ and c₁ are chosen empirically; R(λ₁)is the received radiation at a first wavelength; R(λ₂) is the receivedradiation at a second wavelength; and R(λ₃) is the received radiation ata third wavelength.
 41. The device of claim 40, wherein the wavelengthsare chosen to ensure that the received radiation is substantiallyinsensitive to scattering variations and such that the optical pathlengths through a dermis portion of the tissue location at thewavelengths are substantially equal.
 42. The device of claim 40, whereinthe wavelengths are chosen to ensure that the received radiation fromthe tissue location is substantially insensitive to temperaturevariations, where the wavelengths of the radiation are temperatureisosbestic in the water absorption spectrum or where the wavelengths ofthe received radiation are combined in a way that substantially cancelstemperature dependencies of individual wavelengths of the receivedradiation when computing tissue water fractions.
 43. The device of claim40, wherein the wavelengths are chosen from one of three primary bandsof wavelengths of approximately 1100-1350 nm, approximately 1500-1800nm, and approximately 2000-2300 nm.
 44. The device of claim 40, whereinthe processing device receives and compares at least two sets of opticalmeasurements, where the at least first set of optical measurementscorresponds to the detection of the received radiation whose absorptionis primarily due to water, lipids and non-heme proteins, and where theat least second set of optical measurements corresponds to the detectionof the received radiation whose absorption is primarily due to water,and where a comparison of the at least two optical measurements providesa measure of the absolute water fraction within the tissue location. 45.The device of claim 40, wherein said first, second and third wavelengthsare approximately 1710 nm, approximately 1730 nm and approximately 1740nm, respectively.
 46. A device for determining body fluid-relatedmetrics, the device comprising: a processing device configured toprocess a signal indicative of radiation received from a tissue locationto compute the body fluid-related metrics, wherein received radiationcomprises a plurality of spectral wavelengths chosen to ensure that thecomputed body fluid-related metrics are substantially insensitive toscattering variations and such that the optical path lengths through thetissue location at the wavelengths are substantially equal.
 47. Thedevice of claim 46, wherein the wavelengths are chosen to ensure thatthe received radiation from the tissue location is substantiallyinsensitive to temperature variations, where wavelengths of the receivedradiation are temperature isosbestic in the water absorption spectrum,or where wavelengths of the received radiation are combined in a waythat substantially cancel temperature dependencies of any individualwavelength of the received radiation when computing tissue waterfractions.
 48. The device of claim 46, wherein wavelengths of thereceived radiation are chosen from one of three primary bands ofwavelengths of approximately 1100-1350 nm, approximately 1500-1800 nm,and approximately 2000-2300 nm.
 49. The device of claim 46, wherein theprocessing device receives and compares at least two sets of opticalmeasurements, where the at least first set of optical measurementscorresponds to the detection of the received radiation whose absorptionis primarily due to water, lipids and non-heme proteins, and where theat least second set of optical measurements corresponds to the detectionof the received radiation whose absorption is primarily due to water,and where a comparison of the at least two optical measurements providesa measure of the absolute water fraction within the tissue location. 50.The device of claim 46, wherein the processing device receives andcompares at least two sets of optical measurements, where the at leasttwo sets of optical measurements are based on the received radiationfrom at least two wavelengths and which are combined to form either asingle ratio of the received radiation, a sum of ratios of the receivedradiation, or ratios of ratios of the received radiation.
 51. The deviceof claim 46, wherein the body fluid-related metrics comprise a tissuewater fraction, and where the tissue water fraction (f_(w)) isdetermined such thatf _(w) =c ₁ log[R(λ₁)/R(λ₂)]+c ₀, and where: calibration constants c₀and c₁ are chosen empirically; R(λ₁) is the received radiation at afirst wavelength; and R(λ₂ ) is the received radiation at a secondwavelength.
 52. The device of claim 51, wherein the first and secondwavelengths are approximately 1300 nm and approximately 1168 nm,respectively.
 53. The device of claim 51, wherein the first and secondwavelengths are approximately 1230 nm and approximately 1168 nm,respectively.
 54. The device of claim 46, wherein the body fluid-relatedmetrics comprise a tissue water fraction, and where the tissue waterfraction (f_(w)) is determined such thatf _(w) =c ₂ log[R(λ₁)/R(λ₂)]+c ₁ log[R(λ₂)/R(λ₃)]+c ₀, and where:calibration constants c₀, c₁ and c₂ are chosen empirically; R(λ₁) is thereceived radiation at a first wavelength; R(λ₂) is the receivedradiation at a second wavelength; and R(λ₃) is the received radiation ata third wavelength.
 55. The device of claim 54, wherein the first,second and third wavelengths are approximately 1190 nm, approximately1170 nm, and approximately 1274 nm, respectively.
 56. A device fordetermining body fluid-related metrics, the device comprising: aprocessing device configured to process a signal indicative of radiationreceived from a tissue location compute the body fluid-related metrics,wherein the received radiation comprises a plurality of spectralwavelengths chosen to ensure that the received radiation from the tissuelocation is substantially insensitive to temperature variations, whereinwavelengths of the received radiation are temperature isosbestic in thewater absorption spectrum or wherein the signal is processed in such away that temperature dependencies of individual wavelengths of thereceived radiation is substantially cancelled when computing tissuewater fractions.
 57. The device of claim 56, wherein the wavelengths arechosen from one of three primary bands of wavelengths of approximately1100-1350 nm, approximately 1500-1800 nm, and approximately 2000-2300nm.
 58. The device of claim 56, wherein the processing device receivesand compares at least two sets of optical measurements, where the atleast first set of optical measurements corresponds to the detection ofradiation whose absorption is primarily due to water, lipids andnon-heme proteins, and where the at least second set of opticalmeasurements corresponds to the detection of radiation whose absorptionis primarily due to water, and where a comparison of the at least twooptical measurements provides a measure of the absolute water fractionwithin the tissue location.
 59. The device of claim 56, wherein theprocessing device receives and compares at least two sets of opticalmeasurements, where the at least two sets of optical measurements arebased on the received radiation from at least two wavelengths and whichare combined to form either a single ratio of the received radiation, asum of ratios of the received radiation, or ratios of ratios of thereceived radiation.
 60. The device of claim 56, wherein the bodyfluid-related metrics comprise a tissue water fraction, and where thetissue water fraction (f_(w)) is determined such thatf _(w) =c ₁ log[R(λ₁)/R(λ₂)]+c ₀, and where: calibration constants c₀and c₁ are chosen empirically; R(λ₁) is the received radiation at afirst wavelength; and R(λ₂) is the received radiation at a secondwavelength.
 61. The device of claim 60, wherein the first and secondwavelengths are approximately 1300 nm and approximately 1168 nm,respectively.
 62. The device of claim 60, where the first and secondwavelengths are approximately 1230 nm and approximately 1168 nm,respectively.
 63. The device of claim 56, wherein the body fluid-relatedmetrics comprise a tissue water fraction, and where the tissue waterfraction (f_(w)) is determined such thatf _(w) c ₂ log[R(λ₁)/R(λ₂)]+c ₁ log[R(λ₂)/R(λ₃)]+c ₀, and where:calibration constants c₀, c₁ and c₂ are chosen empirically; R(λ₁) is thereceived radiation at a first wavelength; R(λ₂) is the receivedradiation at a second wavelength; and R(λ₃) is the received radiation ata third wavelength.
 64. The device of claim 63, wherein the first,second and third wavelengths are approximately 1190 nm, approximately1170 nm, and approximately 1274 nm, respectively.